Measles virus selectively blind to signaling lymphocytic activation molecule (SLAM; CD150) is attenuated and induces strong adaptive immune responses in rhesus monkeys

Vincent H J Leonard, Gregory Hodge, Jorge Reyes-Del Valle, Michael B. McChesney, Roberto Cattaneo

Research output: Contribution to journalArticle

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Abstract

The signaling lymphocytic activation molecule (SLAM; CD150) is the immune cell receptor for measles virus (MV). To assess the importance of the SLAM-MV interactions for virus spread and pathogenesis, we generated a wild-type IC-B MV selectively unable to recognize human SLAM (SLAM-blind). This virus differs from the fully virulent wild-type IC-B strain by a single arginine-to-alanine substitution at amino acid 533 of the attachment protein hemagglutinin and infects cells through SLAM about 40 times less efficiently than the isogenic wild-type strain. Ex vivo, this virus infects primary lymphocytes at low levels regardless of SLAM expression. When a group of six rhesus monkeys (Macaca mulatta) was inoculated intranasally with the SLAM-blind virus, no clinical symptoms were documented. Only one monkey had low-level viremia early after infection, whereas all the hosts in the control group had high viremia levels. Despite minimal, if any, viremia, all six hosts generated neutralizing antibody titers close to those of the control monkeys while MV-directed cellular immunity reached levels at least as high as in wild-type-infected monkeys. These findings prove formally that efficient SLAM recognition is necessary for MV virulence and pathogenesis. They also suggest that the selectively SLAM-blind wild-type MV can be developed into a vaccine vector.

Original languageEnglish (US)
Pages (from-to)3413-3420
Number of pages8
JournalJournal of Virology
Volume84
Issue number7
DOIs
StatePublished - Apr 2010
Externally publishedYes

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Measles virus
Adaptive Immunity
Macaca mulatta
Viremia
viremia
Viruses
Haplorhini
monkeys
viruses
pathogenesis
vector vaccines
Cercopithecine Herpesvirus 1
Hemagglutinins
hemagglutinins
Amino Acid Substitution
Neutralizing Antibodies
neutralizing antibodies
Cellular Immunity
cell-mediated immunity
Alanine

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Measles virus selectively blind to signaling lymphocytic activation molecule (SLAM; CD150) is attenuated and induces strong adaptive immune responses in rhesus monkeys. / Leonard, Vincent H J; Hodge, Gregory; Reyes-Del Valle, Jorge; McChesney, Michael B.; Cattaneo, Roberto.

In: Journal of Virology, Vol. 84, No. 7, 04.2010, p. 3413-3420.

Research output: Contribution to journalArticle

Leonard, Vincent H J ; Hodge, Gregory ; Reyes-Del Valle, Jorge ; McChesney, Michael B. ; Cattaneo, Roberto. / Measles virus selectively blind to signaling lymphocytic activation molecule (SLAM; CD150) is attenuated and induces strong adaptive immune responses in rhesus monkeys. In: Journal of Virology. 2010 ; Vol. 84, No. 7. pp. 3413-3420.
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